Abraham had a common question the other day, here it is:
I recently came across this post on the website skeptoid.com. This guy named Brian Dunning says that gluten-free diets aren’t the gato’s meow (on this podcast: http://skeptoid.com/episodes/4239 ). He says that there is no sound evidence for avoiding gluten for general wellness, your thoughts?
I’m drawing a line in the sand with this post.
I cannot devote a response to everyone of of these, I’ll never get anything productive done and, well it’s just boring at some point. So, I’m going to lay out some paramaters for how/if I’ll comment on stuff like this. I will not comment unless the individual is talking about molecular biology mechanism of action in grain intolerance. If I do not see some of these following terms:
I’m not taking the time to comment because the person talking about gluten/grain intolerance can not even sit down at the table for a chat. Mr. Dunning slid in under the wire by mentioning transglutaminase, then misses the boat from there. Let’s look at this from molecular mechanism, then some anthropological data, then a survey of sorts.
Alessio Fasano, MD has put forward a proposed mechanism involving gluten/grains for all autoimmune disease. The scientific American piece is for the lay reader, folks with a scientific background should check this one out:
Scandinavian Journal of Gastroenterology, 2006; 41: 408 Á/419
Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac
Objective. Little is known about the interaction of gliadin with intestinal epithelial cells and the mechanism(s) through which gliadin crosses the intestinal epithelial barrier. We investigated whether gliadin has any immediate effect on zonulin release and signaling. Material and methods. Both ex vivo human small intestines and intestinal cell monolayers were exposed to gliadin, and zonulin release and changes in paracellular permeability were monitored in the presence and absence of zonulin antagonism. Zonulin binding, cytoskeletal rearrangement, and zonula occludens-1 (ZO-1) redistribution were evaluated by immunofluorescence microscopy. Tight junction occludin and ZO-1 gene expression was evaluated by real-time polymerase chain reaction (PCR). Results. When exposed to gliadin, zonulin receptor-positive IEC6 and Caco2 cells released zonulin in the cell medium with subsequent zonulin binding to the cell surface, rearrangement of the cell cytoskeleton, loss of occludin-ZO1 protein Á/protein interaction, and increased monolayer permeability. Pretreatment with the zonulin antagonist FZI/0 blocked these changes without affecting zonulin release. When exposed to luminal gliadin, intestinal biopsies from celiac patients in remission expressed a sustained luminal zonulin release and increase in intestinal permeability that was blocked by FZI/0 pretreatment. Conversely, biopsies from non-celiac patients demonstrated a limited,transient zonulin release which was paralleled by an increase in intestinal permeability that never reached the level of permeability seen in celiac disease (CD) tissues. Chronic gliadin exposure caused down-regulation of both ZO-1 and occludin gene expression. Conclusions. Based on our results, we concluded that gliadin activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules.
Mat Lalonde has helped me stay on top of this stuff. Gluten attaches to the transpost molecule, CXCR3. This causes a release of zonulin which disolves the tight junction between intestinal epithelial cells (enterocytes) and THIS opens the door for autoimmunity and systemic inflammation. Take a second look at that highlighted piece above:
Based on our results, we concluded that gliadin activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules.
Everyone has CXCR3, everyone transports gluten into the enterocytes, everyone experiences gut irritation from gluten. I’ll wager ALL grains, but I’ll get to that later. Now we have evidence that dietary lectins (like gluten) appear to cause insulin resistance:
BMC Endocr Disord. 2005 Dec 10;5:10.Agrarian diet and diseases of affluence–do evolutionary novel dietary lectins cause leptin resistance?
BACKGROUND: The global pattern of varying prevalence of diseases of affluence, such as obesity, cardiovascular disease and diabetes, suggests that some environmental factor specific to agrarian societies could initiate these diseases.
PRESENTATION OF THE HYPOTHESIS: We propose that a cereal-based diet could be such an environmental factor. Through previous studies in archaeology and molecular evolution we conclude that humans and the human leptin system are not specifically adapted to a cereal-based diet, and that leptin resistance associated with diseases of affluence could be a sign of insufficient adaptation to such a diet. We further propose lectins as a cereal constituent with sufficient properties to cause leptin resistance, either through effects on metabolism central to the proper functions of the leptin system, and/or directly through binding to human leptin or human leptin receptor, thereby affecting the function.
TESTING THE HYPOTHESIS: Dietary interventions should compare effects of agrarian and non-agrarian diets on incidence of diseases of affluence, related risk factors and leptin resistance. A non-significant (p = 0.10) increase of cardiovascular mortality was noted in patients advised to eat more whole-grain cereals. Our lab conducted a study on 24 domestic pigs in which a cereal-free hunter-gatherer diet promoted significantly higher insulin sensitivity, lower diastolic blood pressure and lower C-reactive protein as compared to a cereal-based swine feed. Testing should also evaluate the effects of grass lectins on the leptin system in vivo by diet interventions, and in vitro in various leptin and leptin receptor models. Our group currently conducts such studies.
IMPLICATIONS OF THE HYPOTHESIS: If an agrarian diet initiates diseases of affluence it should be possible to identify the responsible constituents and modify or remove them so as to make an agrarian diet healthier.
So, this is a nicely performed clinical trial on pigs, who happen to be great models for human metabolism due to similar endocrine function and the fact they to are opportunistic omnivores. The highlighted piece above is also critical to consider, and where epidemiology shits-the-bed. They put forward a hypothesis, in this case that grain lectins lead to insulin resistance. this was born of the observational studies done with the Kitavans and the fact they developed metabolic problems when upon the introduction of neolithic foods.
So, the pig study is great, how about a human study? Glad you asked:
Diabetologia. 2007 Sep;50(9):1795-807. Epub 2007 Jun 22.A Palaeolithic diet improves glucose tolerance more than a Mediterranean-like diet in individuals with ischaemic heart disease.
AIMS/HYPOTHESIS: Most studies of diet in glucose intolerance and type 2 diabetes have focused on intakes of fat, carbohydrate, fibre, fruits and vegetables. Instead, we aimed to compare diets that were available during human evolution with more recently introduced ones.
METHODS: Twenty-nine patients with ischaemic heart disease plus either glucose intolerance or type 2 diabetes were randomised to receive (1) a Palaeolithic (‘Old Stone Age’) diet (n = 14), based on lean meat, fish, fruits, vegetables, root vegetables, eggs and nuts; or (2) a Consensus (Mediterranean-like) diet (n = 15), based on whole grains, low-fat dairy products, vegetables, fruits, fish, oils and margarines. Primary outcome variables were changes in weight, waist circumference and plasma glucose AUC (AUC Glucose(0-120)) and plasma insulin AUC (AUC Insulin(0-120)) in OGTTs.
So, we have an example of going from an observational theory, to a clinical trial with pigs, to a trial with humans. The Folks fed a Paleo diet showed markedly improved glucose tolerance (they started off Type 2 diabetics, finished “normal”) while the other group, which started as Type 2 diabetics, were fed a grain based Mediterranean diet, showed NO improvement in glucose tolerance.
Back to the original question about Brian Dunnings OPINION about gluten. I see no commentary on any of these mechanisms, no refutation of these findings, no alternate hypothesis that BETTER fits the data at hand. that’s a damn big problem when you go about proclaim “this thing is or is not a problem.”
Now, let’s take a quick look at some anthropological considerations, in this case a comparison of hunter gatherers and agriculturalists. This study is a microcosm of the transition from Hunter Gatherer to Agriculturalist. It twas NOT a good thing for our health. Folks ignorant of this fact…well, it’s like the refrain from law enforcement “Ignorantia juris non excusat-Ignorance of the law does not excuse.” but it DOES result in folks like me needing to actually do the research the Brian should have done before commentating on this subject. Brian takes a stab at an anthropological approach in this way:
The history of human culture is closely tied to the history of bread. Bread was one of our earliest portable foods, which made it possible to take long journeys.
Not trying to be a dick here, but Brian is neglecting those pesky 2-3 million years of human history BEFORE bread. That’s part of the problem, when folks start talking about this stuff. If you are oriented in such as way that evolution via natural selection is not at play, if you think 10,000 years ago was “a long time ago” you are lost. Literally, lost. So, if you want to pull out an anthropological anecdote, you had better frame it in a comprehensive way. Do you think we evolved as vegans? Cool, start at the beginning, build your case and include the tools of the trade: optimum foraging strategy, comparative anatomy, molecular biology etc. But if you throw something out that fits none of the observed data (agriculturalists fared poorly compared to HG’s) and the molecular mechanisms…don’t bother.
One final thing: Social networking “surveys” and N=1 performed millions of times.
I was recently approached by Prof. Cordain and one of his graduate students to make a blog post asking for folks who:
- have been diagnosed with an autoimmune disease,
- ate a paleo diet, and
- put the autoimmunity into remission.
Now, this is at BEST a survey. It shows massive selection bias (how many people have tried paleo and NOT resolved autoimmunity?) but it’s interesting in several ways:
- The resolution of autoimmunity by removing grains and thus reversing gut health is supported by the molecular mechanism I mentioned above.
- No on else (vegans, raw foodists, standard American diet) are reporting resolution of autoimmunity the way the Paleo community is. We are addressing gut health, vit d levels, dysbiosis and stress. All couched from an evolutionary perspective supported by molecular biology.
At the end of Brian’s piece he has the following:
The belief that a gluten-free diet is a good idea anyway has also been studied, and so far the only groups we’ve found that it may actually be somewhat helpful for are patients with Parkinson’s disease, multiple sclerosis, and a few other conditions.
Apparently Brian did not dig very deep as he missed my site, all of the work by Cordain, Lindeberg, Fasano etc. Or he did not do something simple like a google search with a disease like “pancreatitis and gluten” which produced the following:
Rev Esp Enferm Dig. 2008 Dec;100(12):746-51.
[Relapsing acute pancreatitis associated with gluten enteropathy. Clinical, laboratory, and evolutive characteristics in thirty-four patients].
OBJECTIVES: To describe the frequency and the clinical and laboratory characteristics of relapsing acute pancreatitis (AP) associated with gluten enteropathy (GE).
PATIENTS AND METHODS: We prospectively examined all acute pancreatitis cases admitted to our Department in 2006. We recorded a total of 185 patients. With recurring forms, 40 (22%) in all, we used a clinical-lab protocol including serologic and genetic markers, and duodenal biopsy to rule out GE.
RESULTS: A total of 34 patients (18%) met clinical-biological criteria for GE (group1), and were compared to the remaining non-GE AP cases (n=161) (group2). Mean age in the GE group was 54 +/- 25 years, slightly younger than group 2 (61 +/- 14) (NS). There was a mild predominance of women (50%) in group 1 versus group 2 (38.5%) (NS). Seven patients in group 1 (20%) had severe AP, as compared to 27 (17%) in group 2 (NS). The presence of cholelithiasis in group 1 involved 6 cases (18%), which was significantly lower than in group 2–72 cases (45%) (p < 0.05). Four patients with GE developed pseudocysts (12%) versus 13 (8%) in group 2 (NS). Tissue transglutaminase (tTG) was elevated only in 3 patients (9%). Nine patients (34%) were DQ2 (+) and 4 (12%) DQ8 (+); the rest (54%) were all negative for both markers. From an endoscopic perspective there was diffuse duodenitis in 32 patients (95%). Duodenal biopsies revealed villous atrophy (Marsh 3) in 2 patients (6%); submucosal inflammatory infiltration (Marsh 2) in 10 (29.4%); increased intraepithelial lymphocytes (Marsh 1) in 8 cases (23.5%), and normal mucosa (Marsh 0) in 14 patients (41.2%). Response to GFD after 1 year was excellent in 30 patients (88%).
CONCLUSIONS: Relapsing AP with GE represents a relatively common association that is indistinguishable from other APs from a clinical-evolutive standpoint, except for a lower presence of cholelithiasis (p < 0.05). A specific diagnostic protocol is much needed in the identification of these patients since GFD is the only effective therapy to prevent new AP events from developing.
I feel compelled to point out the resources Brian DOES provide for the “gluten is fine” position he seems to be painting. A clinical trial with ambiguous results, and something from Quackwatch. I’ll just bite my tongue on the Quackwatch topic as it just turns into a Straw-man type of scenario. But (and this may be a bit mean) if you are going to label yourself a “skeptic” you had damn well better do some homework.
So Abraham, this is my answer.
It took me all day to put this together, there are 1000 people like Brian posting every day.It feels like a losing battle at times. So, in the future, when someone explains about how a gluten free diet is bogus, if they are literally not worth talking about that is going to be my answer. This piggy-backs on the Neanderthal A Go Go! post. Until something is actually new or important, I’m likely just going to say “I wrote on that” and call it good.